Biopotentials and ionic currents
Biopotentials and ionic currents
The voltage differences which exist between separated points in living cells, tissues, organelles, and organisms are called biopotentials. Related to these biopotentials are ionic charge transfers, or currents, that give rise to much of the electrical changes occurring in nerve, muscle, and other electrically active cells. Electrophysiology is the science concerned with uncovering the structures and functions of bioelectrical systems, including the entities directly related to biological potentials and currents. According to their function, these structures are given descriptive names such as channels, carriers, ionophores, gates, and pumps.
The potential difference measured with electrodes between the interior cytoplasm and the exterior aqueous medium of the living cell is generally called the membrane potential or resting potential (ERP). This potential is usually in the order of several tens of millivolts and is relatively constant or steady. The range of ERP values in various striated muscle cells of animals from insects through amphibia to mammals is about -50 to -100 mV (the voltage is negative inside with respect to outside). Nerve cells show a similar range in such diverse species as squid, cuttlefish, crabs, lobsters, frogs, cats, and humans. Similar potentials have been recorded in single tissue-culture cells.
Biopotentials arise from the electrochemical gradients established across cell membranes. In most animal cells, potassium ions are in greater concentration internally than externally, and sodium ions are in less concentration internally than externally. Generally, chloride ions are in less concentration inside cells than outside cells, even though there are abundant intracellular fixed negative charges. While calcium ion concentration is relatively low in body fluids external to cells, the concentration of ionized calcium internally is much lower (in the nanomolar range) than that found external to the cells.
Measurements of ionic movements through cell membranes of muscle fibers by H. B. Steinbach and by L. A. Heppel in the late 1930s and early 1940s found that radioisotopically labeled sodium ion movement through the cell membrane from inside to outside seemed to depend upon the metabolism of the cell. I. M. Glynn showed that the sodium efflux from red cells depended on the ambient glucose concentration, and A. L. Hodgkin and R. D. Keynes demonstrated in squid and Sepia giant axons that the sodium efflux could be blocked by a variety of metabolic inhibitors (cyanide, 2,4-dinitrophenol, and azide). It was proposed that a metabolic process (sodium pump) located in the cell membrane extruded sodium from the cell interior against an electrochemical gradient. P. C. Caldwell's experiments on the squid's giant axon in the late 1950s indicated that there was a close relation between the activity of the sodium pump and the intracellular presence of high-energy compounds, such as adenosine triphosphate (ATP) and arginine phosphate. Caldwell suggested that these compounds might be directly involved in the active transport mechanism. Evidence by R. L. Post for red cells and by Caldwell for the giant axon also suggested that there was a coupling between sodium extrusion and potassium uptake. Convincing evidence has been presented that ATP breakdown to adenosine diphosphate and phosphorus (ADP + P) provides the immediate energy for sodium pumping in the squid giant axon. It seems that the sodium pump is a sufficient explanation to account for the high internal potassium and the low internal sodium concentrations in nerve, muscle, and red blood cells. See Absorption (biology), Cell permeability
In living cells there are two general types of ion transport processes. In the first, the transported ionic species flows down the gradient of its own electrochemical potential. In the second, there is a requirement for immediate metabolic energy. This first category of bioelectrical events is associated with a class of molecules called channels, embedded in living cell membranes. It is now known that cell membranes contain many types of transmembrane channels. Channels are protein structures that span the lipid bilayers forming the backbones of cell membranes. The cell membranes of nerve, muscle, and other tissues contain ionic channels. These ionic channels have selectivity filters in their lumens such that in the open state only certain elementary ion species are admitted to passage, with the exclusion of other ion species. See Cell membranes
There are two general types of channels, and these are classified according to the way in which they respond to stimuli. Electrically excitable channels have opening and closing rates that are dependent on the transmembrane electric field. Chemically excitable channels (usually found in synaptic membranes) are controlled by the specific binding of certain activating molecules (agonists) to receptor sites associated with the channel molecule.
Calcium channels are involved in synaptic transmission. When a nerve impulse arrives at the end of a nerve fiber, calcium channels open in response to the change in membrane potential. These channels admit calcium ions, which act on synaptic vesicles, facilitating their fusion with the presynaptic membrane. Upon exocytosis, these vesicles release transmitter molecules, which diffuse across the synaptic cleft to depolarize the postsynaptic membrane by opening ionic channels. Transmitter activity ceases from the action of specific transmitter esterases or by reabsorption of transmitter back into vesicles in the presynaptic neuron. Calcium channels inactivate and close until another nerve impulse arrives at the presynaptic terminal. Thus biopotentials play an important role in both the regulation and the genesis of synaptic transmission at the membrane channel level.
Ionic currents flow through open channels. The ion impermeable membrane lipid bilayer acts as a dielectric separating two highly conductive salt solutions. Ionic channels have the electrical property of a conductance between these solutions. The membrane conductance at any moment depends on the total number of channels, the type of channels, the fraction of channels found in the open state, and the unit conductances of these open channels. The most common channels directly giving rise to biopotentials are those admitting mainly sodium ions, potassium ions, chloride ions, or calcium ions. These channels are named after the predominant charge carrier admitted in the open state, such as potassium channels. It is now known that there are charged amino acid groups lining the channel lumen that determine the specificity of the channel for particular ions. These selectivity filters admit only ions of the opposite charge.
Hodgkin and A. F. Huxley proposed in 1952 that there were charged molecular entities responsible for the opening and closing of the ionic conductance pathways. These structures had to be charged to be able to move in response to changing electrical forces when the membrane voltage changed. Any movement of the gating structures would require a movement of charge and hence should have a detectable component of current flow across the membrane. It was not until 1973 that the existence of a gating current in squid axon sodium channels was demonstrated, and gating currents and their significance became a lively endeavor in membrane biophysics. See Biophysics